Prostacyclin (PGI.sub.2) of the following structure is of various pharamological effects including blood platelet agglutination inhibitory activity and vasodilation activity, and is considered to be promising for development of medicine. However, prostacyclin has such a drawback, on the other hand, that it is a very unstable compound. ##STR1##
Of the prostacyclin derivatives, carbacyclin (called 9(O)-methanoprostacyclin) of the following structure has been known to be a chemically stable compound in which the oxygen atom of enol ether moiety of prostacyclin (PGI.sub.2) is substituted with a methylene group. ##STR2##
Processes for the synthesis of an optically active carbacyclin have been disclosed, for example, in "Tetrahedron", Vol. 37, 4391 (1981), "Journal of Organic Chemistry", Vol. 44, 2880 (1979) and "Journal of Organic Chemistry", Vol. 46, 1954 (1981). However, these processes are of the disadvantage of lengthy steps. Furthermore, processes for the synthesis of the above-mentioned carbacyclin using as an intermediate (1SR,5RS)-7,7-ethylenedioxy-2-ethoxycarbonyl-cis-bicyclo[3.3.0]octan-3-one represented by the following formula (II)' are disclosed, for example, in "Tetrahedron Letters", 3743 (1978), "Journal of Chemical Society, Chemical Communication", 1067 (1978) and "Tetrahedron Letters", 433 (1979). ##STR3## However, the products obtained by the above-mentioned processes are racemic compounds, i.e., the (1SR,5RS) epimers which do not exhibit optical activity. That is, since the intermediates used in these processes are racemic compounds, the products obtained thereby are necessarily racemic compounds. Accordingly, if the optically active (1S,5R) compound can be used as the intermediate in the above-mentioned processes, it follows that the optically active carbacyclin referred to above is obtained quite conveniently.
It has been known in this connection that the above-mentioned intermediate, the compound of the formula (II)' is prepared from cis-bicyclo[3.3.0]octane-3,7-dione of the following formula (V)' according to the following scheme as taught in the above-mentioned "Journal of Chemical Society, Chemical Communication", 1067 (1978) and "Tetrahedron Letters", 433 (1979). ##STR4##
As can be seen from the above scheme, the compound of the formula (II)' which is formed by introduction of an ethoxycarbonyl group into the compound of the formula (IV)' always becomes a racemic compound which does not have optical activity. Thus, these prior art processes have involved such a decisive problem that because of very close similarities in chemical behavior and physical properties between the optically active substances constituting this racemic compound, i.e. the (1S,5R) epimer and the (1R,5S) epimer, the compound (II)' cannot be resolved by means of an ordinary optical resolution. In this light, the (1S,5R) and (1R,5S) epimers can be said to be new substances which did not exist as an independently isolated compound.
Under such circumstances, we had come to such an idea that an optically active carbacyclin can be prepared by a simple process using only the (1S,5R) epimer, i.e. a compound represented by the following formula (I)', if said (1S,5R) epimer can be isolated from the above-mentioned compound (II)'. ##STR5## After extensive researches, we have found that the simple process can be accomplished by a unique utilization of microorganisms.